tbuckley/cabot-search huggingface dataset:
SKYSCRAPER-02: Primary results of a phase III, randomized, double-blind, placebo-controlled study of atezolizumab (atezo) + carboplatin + etoposide (CE) with or without tiragolumab (tira) in patients (pts) with untreated extensive-stage small cell lung cancer (ES-SCLC).
Authors: Charles M. Rudin, Stephen V. Liu, Shun Lu, Ross A. Soo, Min Hee Hong, Jong-Seok Lee, Maciej Bryl, Daphne W Dumoulin, Achim Rittmeyer, Chao-Hua Chiu, Ozgur Ozyilkan, Alejandro Navarro, Silvia Novello, Yuichi Ozawa, Raymond Meng, Tien Hoang, Anthony Lee, Xiaohui Wen, Meilin Huang, Martin Reck
Journal: Journal of Clinical Oncology (2022)

LBA8507 Background: Atezo, in combination with CE, was the first cancer immunotherapy approved for 1L treatment of ES-SCLC. However, most pts eventually experience disease progression. TIGIT is a novel inhibitory immune checkpoint present on activated T cells and NK cells. Tira (anti-TIGIT) may synergise with other immunotherapies, such as PD-L1/PD-1 inhibitors, and further amplify the immune response to improve clinical outcomes. SKYSCRAPER-02 (NCT04256421) evaluates whether the antitumor effect and survival benefits of the combination of atezo + CE could be enhanced by adding tira in pts with ES-SCLC. Methods: Eligible pts with untreated ES-SCLC (asymptomatic treated or untreated brain metastases [BM] permitted) were randomized 1:1 to receive induction tira 600 mg IV or placebo (pbo) combined with atezo 1200 mg IV + CE for 4 x 21-day cycles followed by maintenance tira or placebo combined with atezo every 3 weeks until disease progression or loss of clinical benefit. Stratification factors include ECOG PS (0 vs 1); presence/history of BM (yes vs no); LDH (≤upper limit of normal [ULN] vs &gt;ULN). Co-primary endpoints were investigator-assessed PFS and OS in all randomized pts without the history/presence of BM at baseline (primary analysis set [PAS]). Additional endpoints include PFS and OS in all randomized pts regardless of BM status (full analysis set [FAS]), objective response rate, duration of response, and safety. Results: A total of 490 patients were randomized (tira + atezo + CE, n=243; pbo + atezo + CE, n=247). As of 6 Feb 2022, median duration of follow-up was 13.9 months (mo); data represent final analysis for PFS and interim analysis for OS. In the PAS, no additional benefit was seen for tira + atezo + CE in PFS or OS compared with pbo + atezo + CE (Table). PFS and OS in the FAS were consistent with those observed in the PAS (Table). Grade 3/4 TRAEs occurred in 52.3% (tira + atezo + CE) and 55.7% (pbo + atezo + CE) and Grade 5 TRAEs occurred in 0.4% (tira + atezo + CE) and 2.0% (pbo + atezo + CE). TRAEs leading to any treatment discontinuation occurred in 5.0% and 5.3% with tira + atezo + CE and pbo + atezo + CE, respectively. Conclusions: The addition of tira to atezo + CE did not provide benefit over atezo + CE in pts with untreated ES-SCLC with or without BM. The combination was well tolerated, and no new safety signals were identified. The study will continue to planned final OS analysis. Clinical trial information: NCT04256421. [Table: see text]
VCAM-1-binding peptide targeted cationic liposomes containing NLRP3 siRNA to modulate LDL transcytosis as a novel therapy for experimental atherosclerosis
Authors: Xiong Jia, Xiangli Bai, Xiaoyan Yang, Ling Wang, Yajing Lu, Lin Zhu, Ying Zhao, Wenzhuo Cheng, Meng Shu, Qiyong Mei, Si Jin
Journal: Metabolism (2022)
The impact of diabetes on postoperative outcomes following spine surgery: A meta-analysis of 40 cohort studies with 2.9 million participants
Authors: Mingjiang Luo, Qi Cao, Di Wang, Ridong Tan, Yuxin Shi, Jiang Chen, Rong Chen, Guojun Tang, Liangyuan Chen, Zubing Mei, Zhihong Xiao
Journal: International Journal of Surgery (2022)
Murine macrophages or their secretome delivered in alginate dressings enhance impaired wound healing in diabetic mice
Authors: Georgios Theocharidis, Sahar Rahmani, Sangmin Lee, Zhuqing Li, Antonio Lobao, Konstantinos Kounas, Xanthi-Lida Katopodi, Peng Wang, Salina Moon, Ioannis S. Vlachos, Monika Niewczas, David Mooney, Aristidis Veves
Journal: Biomaterials (2022)
Surgical outcomes and sexual function after laparoscopic colon cancer surgery with transvaginal versus conventional specimen extraction: A retrospective propensity score matched cohort study
Authors: Mingguang Zhang, Xiyue Hu, Xu Guan, Wei Zheng, Zheng Liu, Zheng Jiang, Jianqiang Tang, Xishan Wang
Journal: International Journal of Surgery (2022)

Natural orifice specimen extraction has been shown to reduce postoperative pain and wound complications, and provide better cosmetic outcome. However, whether transvaginal specimen extraction affects sexual function remains controversial. The purpose of this study was to investigate the short-term outcomes, sexual function, cosmetic outcomes and prognosis after colon cancer surgery with transvaginal specimen extraction.This study was a propensity score-matched comparative retrospective study, based on prospectively collected data in a single center. This study included 70 pairs of propensity score-matched female patients who underwent laparoscopic curative resection for stage I-III colon cancer with transvaginal specimen extraction and conventional specimen extraction between November 2015 and November 2020. Covariates used in the propensity score included age, tumor diameter, tumor differentiation, T stage and American Joint Committee on Cancer stage. Outcome measures included postoperative complication, postoperative sexual function, cosmetic result, disease-free survival and overall survival.Patients in transvaginal group were administered with less additional analgesics (P = 0.008), and had fewer wound complications (P = 0.028). None of patient in the two groups underwent anastomotic leakage, incisional disruption or vaginal fistula. The baseline pre-operative Female Sexual Function Index scores in two groups were the same, and no difference was found in postoperative score between the two groups (P = 0.790). The cosmetic score was significantly better in transvaginal group than that of conventional laparoscopy group (P = 0.000). During the follow-up period, there were no differences in OS or DFS between the two groups (P = 0.658, P = 0.663).Compared with laparoscopic colon cancer radical resection with specimen extraction, transvaginal specimen extraction is oncologically safe, brings better short-term outcomes, improved cosmetic results and has limited adverse effect on female's sexual function. This procedure can be further carried out in more appropriate patients.
Protective properties of polyphenols in food allergy: A review
Authors: Binghui Zeng, Tianyi Jiang, Wenwen Xiong, Huilian Che, Shengqian Sun
Journal: Allergy (2022)

Supinfo Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Correction: hUC-EVs-ATO reduce the severity of acute GVHD by resetting inflammatory macrophages toward the M2 phenotype
Authors: Yan Su, Xueyan Sun, Xiao Liu, Qingyuan Qu, Liping Yang, Qi Chen, Fengqi Liu, Yueying Li, Qianfei Wang, Bo Huang, Xiao-Hui Zhang, Xiao-Jun Huang
Journal: Journal of Hematology & Oncology (2022)
Time‐dependent prediction of mortality and cytomegalovirus reactivation after allogeneic hematopoietic cell transplantation using machine learning
Authors: Lisa Eisenberg, Christian Brossette, Jochen Rauch, Andrea Grandjean, Hellmut Ottinger, Jürgen Rissland, Ulf Schwarz, Norbert Graf, Dietrich W. Beelen, Stephan Kiefer, Nico Pfeifer, Amin T. Turki
Journal: American Journal of Hematology (2022)

Abstract Allogeneic hematopoietic cell transplantation (HCT) effectively treats high‐risk hematologic diseases but can entail HCT‐specific complications, which may be minimized by appropriate patient management, supported by accurate, individual risk estimation. However, almost all HCT risk scores are limited to a single risk assessment before HCT without incorporation of additional data. We developed machine learning models that integrate both baseline patient data and time‐dependent laboratory measurements to individually predict mortality and cytomegalovirus (CMV) reactivation after HCT at multiple time points per patient. These gradient boosting machine models provide well‐calibrated, time‐dependent risk predictions and achieved areas under the receiver‐operating characteristic of 0.92 and 0.83 and areas under the precision–recall curve of 0.58 and 0.62 for prediction of mortality and CMV reactivation, respectively, in a 21‐day time window. Both models were successfully validated in a prospective, non‐interventional study and performed on par with expert hematologists in a pilot comparison.
Robust Dual Enzyme Cascade‐Catalytic Cholesterol Depletion for Reverse Tumor Multidrug Resistance
Authors: Jialing Guo, Xiaoming Du, Jingshu Huang, Chenxin Liu, Yingying Zhou, Ying Li, Bin Du
Journal: Advanced Healthcare Materials (2022)

Although combination drugs and P-glycoprotein inhibitors are the main methods to solve multidrug resistance, these methods ignore the pathological structure of drug-resistant cells and extremely limit curative effect. Herein, a new paradigm of reversing multidrug resistance with abnormal expression of cholesterol as the target is proposed, which uses the cascade catalysis of "natural enzyme" cholesterol oxidase (COD) and "nanoenzyme" Cu2+ -modified zirconium-based metal-organic framework (ZrMOF(Cu)) to convert cholesterol into the highly cytotoxic hydroxyl radicals. The doxorubicin (DOX)-loaded nanoparticles (DOX@COD-MOF) can significantly reduce the cholesterol content of cancer cells via COD, which decrease the rigidity of drug resistant cancer cell membranes and restore the sensitivity of multidrug-resistant cells to DOX. Afterward, DOX@COD-MOF is encapsulated by cancer cell membranes (CCM) to construct a bionic "dual enzyme catalytic cascade nanoreactor" (DOX@COD-MOF@CCM). Such a rational design presents a preferential accumulation tendency to tumor sites due to the homologous targeting mechanism of CCM, and affords 94.4% in tumor growth suppression without systemic toxicity in vivo. This work aims to achieve the therapeutic purpose of high efficiency and low toxicity. It has the characteristics of "converting enemy into friend, " and opens up a promising way for effectively reversing multidrug resistance of tumors.
Rapid sterilisation and diabetic cutaneous regeneration using cascade bio-heterojunctions through glucose oxidase-primed therapy
Authors: Yi Deng, Xumei Ouyang, Jiyu Sun, Xiuyuan Shi, Yunfei Li, Yau Kei Chan, Weizhong Yang, Shaojun Peng
Journal: Bioactive Materials (2022)

The cutaneous wound in diabetic patients frequently encounters intractable pathogenic infections due to the hyperglycemia micromilieu which is conducive to bacterial growth and multiplication. Despite the extensive clinical use of antibiotics to treat bacterial infections, the emergence of drug-resistant and super pathogens as well as the potential side effects of antibiotics have elicited alarming challenges to public health. To address this daunting concern, we devise and develop a photo-activated cascade bio-heterojunctions (C-bio-HJs) for rapid sterilization and diabetic cutaneous regeneration. In the designed C-bio-HJs, photo-generated electron-hole pairs of graphite-phase carbon nitride (g-C3N4) are effectively separated with the marriage of molybdenum disulfide (MoS2), which achieves the augmented photodynamic antibacterial effect. Moreover, glucose oxidase (GOx) tethered on the bio-HJs catalyzes glucose into hydrogen peroxide (H2O2) in diabetic wounds for starvation therapy. Furthermore, Mo4+ enables the catalysis of H2O2 into a highly effective hydroxyl radical (·OH) for chemodynamic-photothermal combined antibacterial therapy. Both in vitro and in vivo results authenticate the cascading antibacterial properties and skin regeneration-promoting effects of the C-bio-HJs, which provide a facile strategy to combat diabetic wound healing through the synergistic GOx-primed dynamic therapies.
HCC EV ECG score: An extracellular vesicle‐based protein assay for detection of early‐stage hepatocellular carcinoma
Authors: Na Sun, Ceng Zhang, Yi‐Te Lee, Benjamin V. Tran, Jing Wang, Hyoyong Kim, Junseok Lee, Ryan Y. Zhang, Jasmine J. Wang, Junhui Hu, Zhicheng Zhang, Manaf S. Alsudaney, Kuan‐Chu Hou, Hubert Tang, Tiffany X. Zhang, Icy Y. Liang, Ziang Zhou, Mengxiang Chen, Angela Hsiao‐Jiun Yeh, Wenyuan Li, Xianghong Jasmine Zhou, Helena R. Chang, Steven‐Huy B. Han, Saeed Sadeghi, Richard S. Finn, Sammy Saab, Ronald W. Busuttil, Mazen Noureddin, Walid S. Ayoub, Alexander Kuo, Vinay Sundaram, Buraq Al‐Ghaieb, Juvelyn Palomique, Kambiz Kosari, Irene K. Kim, Tsuyoshi Todo, Nicholas N. Nissen, Maria Lauda Tomasi, Sungyong You, Edwin M. Posadas, James X. Wu, Madhuri Wadehra, Myung‐Shin Sim, Yunfeng Li, Hanlin L. Wang, Samuel W. French, Shelly C. Lu, Lily Wu, Renjun Pei, Li Liang, Ju Dong Yang, Vatche G. Agopian, Hsian‐Rong Tseng, Yazhen Zhu
Journal: Hepatology (2022)

The sensitivity of current surveillance methods for detecting early-stage hepatocellular carcinoma (HCC) is suboptimal. Extracellular vesicles (EVs) are promising circulating biomarkers for early cancer detection. In this study, we aim to develop an HCC EV-based surface protein assay for early detection of HCC.Tissue microarray was used to evaluate four potential HCC-associated protein markers. An HCC EV surface protein assay, composed of covalent chemistry-mediated HCC EV purification and real-time immuno-polymerase chain reaction readouts, was developed and optimized for quantifying subpopulations of EVs. An HCC EV ECG score, calculated from the readouts of three HCC EV subpopulations ( E pCAM + CD63 + , C D147 + CD63 + , and G PC3 + CD63 + HCC EVs), was established for detecting early-stage HCC. A phase 2 biomarker study was conducted to evaluate the performance of ECG score in a training cohort ( n = 106) and an independent validation cohort ( n = 72).Overall, 99.7% of tissue microarray stained positive for at least one of the four HCC-associated protein markers (EpCAM, CD147, GPC3, and ASGPR1) that were subsequently validated in HCC EVs. In the training cohort, HCC EV ECG score demonstrated an area under the receiver operating curve (AUROC) of 0.95 (95% confidence interval [CI], 0.90-0.99) for distinguishing early-stage HCC from cirrhosis with a sensitivity of 91% and a specificity of 90%. The AUROCs of the HCC EV ECG score remained excellent in the validation cohort (0.93; 95% CI, 0.87-0.99) and in the subgroups by etiology (viral: 0.95; 95% CI, 0.90-1.00; nonviral: 0.94; 95% CI, 0.88-0.99).HCC EV ECG score demonstrated great potential for detecting early-stage HCC. It could augment current surveillance methods and improve patients' outcomes.
Cellular communication network 2 (connective tissue growth factor) aggravates acute DNA damage and subsequent DNA damage response-senescence-fibrosis following kidney ischemia reperfusion injury
Authors: Floris A. Valentijn, Sebastiaan N. Knoppert, Laura Marquez-Exposito, Raúl R. Rodrigues-Diez, Georgios Pissas, Jiaqi Tang, Lucia Tejedor-Santamaria, Roel Broekhuizen, Rohan Samarakoon, Theodoros Eleftheriadis, Roel Goldschmeding, Tri Q. Nguyen, Marta Ruiz-Ortega, Lucas L. Falke
Journal: Kidney International (2022)

Chronic allograft dysfunction with progressive fibrosis of unknown cause remains a major issue after kidney transplantation, characterized by ischemia-reperfusion injury (IRI). One hypothesis to account for this is that spontaneous progressive tubulointerstitial fibrosis following IRI is driven by cellular senescence evolving from a prolonged, unresolved DNA damage response (DDR). Since cellular communication network factor 2 ((CCN2), formerly called connective tissue growth factor), an established mediator of kidney fibrosis, is also involved in senescence-associated pathways, we investigated the relation between CCN2 and cellular senescence following kidney transplantation. Tubular CCN2 overexpression was found to be associated with DDR, loss of kidney function and tubulointerstitial fibrosis in both the early and the late phase in human kidney allograft biopsies. Consistently, CCN2 deficient mice developed reduced senescence and tubulointerstitial fibrosis in the late phase; six weeks after experimental IRI. Moreover, tubular DDR markers and plasma urea were less elevated in CCN2 knockout than in wild-type mice. Finally, CCN2 administration or overexpression in epithelial cells induced upregulation of tubular senescence-associated genes including p21, while silencing of CCN2 alleviated DDR induced by anoxia-reoxygenation injury in cultured proximal tubule epithelial cells. Thus, our observations indicate that inhibition of CCN2 can mitigate IRI-induced acute kidney injury, DNA damage, and the subsequent DDR-senescence-fibrosis sequence. Hence, targeting CCN2 might help to protect the kidney from transplantation-associated post-IRI chronic kidney dysfunction.
Robust neutralizing antibody responses after single-dose BNT162b2 vaccination at long intervals from prior SARS-CoV-2 infection and ceiling effect with repeated vaccination
Authors: Ji Yun Noh, Hee Jin Cheong, Woo Joo Kim, Ju-Yeon Choi, Hye Won Lee, Sung Soon Kim, Byoungguk Kim, Joon Young Song
Journal: Journal of Infection (2022)
A tribute to Marc Caron (1946–2022)
Authors: Bryan Roth
Journal: Journal of Clinical Investigation (2022)

Neuroscience lost an exceptional leader in molecular neurobiology when Marc G. Caron, PhD, passed away April 25, 2022, at the age of 75 (Figure 1).Marc's contributions to our understanding of G proteincoupled receptors generally, and dopamine receptors in particular, span nearly 50 years.Marc's major accomplishments include the identification of dopamine receptors as regulating prolactin release (1) and being G protein coupled (2); molecular cloning of several dopamine receptors and transporters (3-5); identification of arrestin as a major mediator of GPCR signaling (6); and, in systematic studies, demonstrating the roles of various dopamine receptors and transporters in vivo via the use of mice with genetically deleted receptors and transporters (7, 8).Together with his long-time collaborator Robert (Bob) Lefkowitz (who received the Nobel Prize in Chemistry in 2012), Marc also made seminal contributions to our current understanding of GPCRs in normal and abnormal physiology.Marc's work was instrumental in clarifying the role of dopamine receptors in substance use disorders as well as neuropsychiatric conditions and therapeutics (9, 10).Moreover, his work on β-arrestin signaling of GPCRs has enormous clinical implications related to drug development, including serving as the basis for biased analgesic ligands with lower potential for patient misuse (7).Marc published more than 650 papers, and his work, collectively, received nearly 140,000 citations.Marc was a true giant in the field of GPCR research, and he will be missed greatly by the scientific community.
IgE-neutralizing UB-221 mAb, distinct from omalizumab and ligelizumab, exhibits CD23-mediated IgE downregulation and relieves urticaria symptoms
Authors: Be-Sheng Kuo, Chao-Hung Li, Jiun-Bo Chen, Yu-Yu Shiung, Chia-Yu Chu, Chih-Hung Lee, Yaw-Jen Liu, Je-Hung Kuo, Cindy Hsu, Hsiao-Wen Su, Ywan-Feng Li, Annie Lai, Yueh-Feng Ho, Yi-Ning Cheng, Hong-Xuan Huang, Meng-Chung Lung, Ming-Syue Wu, Fu-Hong Yang, Chen-Han Lin, William Tseng, Jasper Yang, Chia-Yin Lin, Pei-Hua Tsai, Heng-Kwei Chang, Yi-Jen Wang, Techeng Chen, Shugene Lynn, Mei-June Liao, Chang Yi Wang
Journal: Journal of Clinical Investigation (2022)

Over the last 2 decades, omalizumab is the only anti-IgE antibody that has been approved for asthma and chronic spontaneous urticaria (CSU). Ligelizumab, a higher-affinity anti-IgE mAb and the only rival viable candidate in late-stage clinical trials, showed anti-CSU efficacy superior to that of omalizumab in phase IIb but not in phase III. This report features the antigenic-functional characteristics of UB-221, an anti-IgE mAb of a newer class that is distinct from omalizumab and ligelizumab. UB-221, in free form, bound abundantly to CD23-occupied IgE and, in oligomeric mAb-IgE complex forms, freely engaged CD23, while ligelizumab reacted limitedly and omalizumab stayed inert toward CD23; these observations are consistent with UB-221 outperforming ligelizumab and omalizumab in CD23-mediated downregulation of IgE production. UB-221 bound IgE with a strong affinity to prevent FcԑRI-mediated basophil activation and degranulation, exhibiting superior IgE-neutralizing activity to that of omalizumab. UB-221 and ligelizumab bound cellular IgE and effectively neutralized IgE in sera of patients with atopic dermatitis with equal strength, while omalizumab lagged behind. A single UB-221 dose administered to cynomolgus macaques and human IgE (ε, κ)–knockin mice could induce rapid, pronounced serum-IgE reduction. A single UB-221 dose administered to patients with CSU in a first-in-human trial exhibited durable disease symptom relief in parallel with a rapid reduction in serum free-IgE level.
Does immune destruction drive all forms of bone marrow failure?
Authors: Brian M. Dulmovits, Timothy S. Olson
Journal: Journal of Clinical Investigation (2022)

Current paradigms of bone marrow failure (BMF) pathophysiology suggest that immune-mediated destruction of hematopoietic stem and progenitor cells (HSPCs) drives acquired aplastic anemia. In contrast, loss of HSPCs due to senescence and/or apoptosis causes BMF in inherited BMF syndromes. In this issue of the JCI, Casado and colleagues challenge this dichotomous conception by demonstrating that NK cell-dependent, immune-mediated hematopoietic suppression and HSPC clearance drive BMF in Fanconi anemia (FA). They show that genotoxic stress upregulates natural killer group 2 member D ligands (NKG2D-L) on FA HSPCs leading to NK cell cytotoxicity through NKG2D receptor activation. Inhibition of NKG2D-NKG2D-L interactions enhanced FA HSPC clonogenic potential and improved cytopenias in vivo. These results provide alternative targets for the development of immunosuppressive therapies to reduce HSPC loss and mitigate the risk of hematologic malignancies in FA.
Data we can trust
Authors: Sarah Jackson, Corinne L. Williams, Kathleen L. Collins, Elizabeth M. McNally
Journal: Journal of Clinical Investigation (2022)

"On behalf of all authors of the submission, I warrant that the work is original and scientifically accurate ..." If you've submitted a manuscript to the Journal of Clinical Investigation or JCI Insight, this phrase should sound familiar. This statement is the very first thing that we ask authors to verify for every new submission. While this may seem like a simple formality or just another screen to click through, certifying the accuracy of information presented to the journal is essential to the publishing process and scientific integrity. Data accuracy forms the foundation of the scientific enterprise, and without it, the enterprise risks crumbling.
Taking cues from convalescence to improve vaccines against hepatitis C virus
Authors: Bharath K. Sreekumar, Taha Y. Taha, Melanie Ott
Journal: Journal of Clinical Investigation (2022)

Hepatitis C virus (HCV) infection remains a worldwide public health issue despite direct-acting antivirals. A substantial proportion of infected individuals (15%-45%) spontaneously clear repeated HCV infections with genetically different viruses by generating broadly neutralizing antibodies (bNAbs). However, translating this response into an effective vaccine strategy has been unsuccessful. In this issue of the JCI, Frumento and colleagues report on their study of bNAb evolution longitudinally in convalescent individuals with repeated infections. Using pseudotyped viruses, well-characterized monoclonal antibodies, and complex modeling, the authors show that multiple exposures to antigenically related, antibody-sensitive viral envelope proteins induced potent bNAbs. This work provides valuable insight into the best strategies for developing HCV vaccines in the future that may successfully reproduce the immunity induced during natural exposures.